COMMUNICATION
DOI: 10.1002/chem.201100192
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Bu4NI-Catalyzed C O Bond Formation by Using a Cross-Dehydrogenative
Coupling (CDC) Reaction
Long Chen,[a] Erbo Shi,[a] Zhaojun Liu,[a] Shulin Chen,[a] Wei Wei,[a] Hong Li,[a]
Kai Xu,[a] and Xiaobing Wan*[a, b]
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The cleavage and functionalization of C H bonds is of
catalytic formation of C O bonds through C H functionali-
zation under transition-metal-free conditions is less ex-
plored.[8]
fundamental interest for both academia and industry. Gener-
ally, the transformation relies on transition metals,[1] which
are involved in four major approaches: 1) electrophilic acti-
a-Acyloxy ethers appear frequently as a structural unit[9]
in biological and medicinal molecules of interest and are
also useful synthetic intermediates[10] in organic synthesis.
(Scheme 1) Conventional routes to this ubiquitous class of
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vation of the C H bond by a high-valent transition metal;
2) oxidative addition to the C H bond by low-valent transi-
tion metals; 3) C H bond activation by s-bond metathesis,
and 4) insertion of a metal carbenoid/nitrenoid into the C
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H bond. After extensive studies, transition-metal-catalyzed
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C H activation has arisen as an excellent synthetic method
to build complex structures because it reduces prefunction-
alization while improving atom economy and energy effi-
ciency. However, the use of expensive metal catalysts and
the problems involved in removing the residual metals from
the final products, which is usually a difficult and tedious
process, limits the practical applications of this strategy. The
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discovery of an efficient C H transformation that does not
Scheme 1. Selected examples of a-acyloxy ethers.
require a metal catalyst would be of great value. This strat-
egy would eliminate the requirement to remove traces of
metal from the final products and solve the problem of dis-
posal of the metal catalyst from the reaction mixtures. Re-
compounds have relied on the addition of a carboxylic acid
to an alkenyl ether,[11] the nucleophilic substitution of a car-
boxylic acid to an a-halo ether,[12] the esterification of a
hemiacetal,[9b,e,13] or a two-step synthesis.[14] Herein, we
report a simple and efficient method to construct a-acyloxy
ethers by using Bu4NI as a catalyst and tert-butyl hydroper-
oxide (TBHP) as the oxidant. The transformation involves
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cently, several groups disclosed a variety of novel C C bond
formations by using C H activation under transition-metal-
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free conditions.[2,3] The cross-dehydrogenative coupling
(CDC) reaction, beyond traditional cross-couplings, has
been the object of increasing interest over the last ten years.
However, transition-metal catalysts, such as iron and copper
salts, were usually required to promote this transforma-
tion.[4,5]
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the CDC reaction of the C H bond and the O H group,
without the aid of a transition-metal catalyst.
We began our investigation by examining the coupling of
benzoic acid (1a) and 1,4-dioxane (2a) under metal-free
conditions (Table 1, entry 1). From a wide range of candi-
dates, the combination of Bu4NI (20 mol%) and TBHP
(2.2 equiv, 70% aqueous solution) was found to be particu-
larly effective and produced the desired 1,4-dioxan-2-yl ben-
zoate (3a) in 95% yield. Table 1 shows the impact of cata-
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The formation of C O bonds is a fundamental transfor-
mation in synthetic organic chemistry.[6] Therefore, the cata-
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lytic use of transition metals in C O construction through
C H functionalization is of great interest. However, the
[7]
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[a] L. Chen, E. Shi, Z. Liu, S. Chen, W. Wei, H. Li, K. Xu,
Prof. Dr. X. Wan
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lyst and oxidant on the efficiency of the C H oxidation pro-
cess. The choice of oxidant has a paramount effect on this
transformation; replacing TBHP with other common oxi-
dants halted the formation of the desired product (Table 1,
entries 2–8). In the absence of Bu4NI, no 3a was formed
(Table 1, entry 10). Other quaternary ammonium iodides,
such as Me4NI and Me3BnNI, were also tested resulting in
the desired product 3a in decreased yields (Table 1, en-
tries 11 and 12). Both Bu4NCl and Bu4NBr showed negligi-
ble activity (Table 1, entries 13 and 14). Notably, the addi-
Key Laboratory of Organic Synthesis of Jiangsu Province
College of Chemistry, Chemical Engineering and Materials Science
Soochow (Suzhou) University, Suzhou 215123 (P.R. China)
Fax : (+86)512-6588-0334
[b] Prof. Dr. X. Wan
State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000 (China)
Supporting information for this article is available on the WWW
Chem. Eur. J. 2011, 17, 4085 – 4089
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4085